Synaptic activity is central to all behavior, learning, and memory; synaptic dysfunction leads to neurological disorders such as epilepsy, autism, Alzheimer's disease, depression, and sleep disorders. Developing new therapeutic approaches for preventing or treating synaptic dysfunction requires a continuing cadre of young investigators well-trained in multidisciplinary techniques to address synaptic function. This application requests five years of continued funding for the Synapse Neurobiology Training Program (SNTP), to support 4 predoctoral trainees per year, selected from a pool of highly qualified applicants in years 3-5 of thesis research relevant to synaptic structure and function. Research on synaptic function and dysfunction are strengths of the 20 SNTP faculty mentors. In the first 4 years of the SNTP, 11 trainees received individualized, in-depth, multidisciplinary training, 3 have completed their PhD degree and are engaged in academic research, biotech, and teaching careers. In addition, 6 new faculty members were recruited to the Department of Neuroscience, expanding and strengthening the multifaceted research approaches being taught to SNTP trainees and providing a rich diversity of thesis research labs investigating synapse neurobiology and synaptic disorders. SNTP trainees have access to cutting-edge tools and training in a wide array of research approaches via the NINDS-funded Center for Neuroscience Research Cores (Imaging, Behavior, Genomics, and Electrophysiology). The SNTP is further strengthened by a new, stand-alone Neuroscience Program and a curriculum that increases the depth and breadth of trainees' exposure to fundamental concepts in neuroscience, with particular emphasis on the synapse. The new curriculum shifts focus from lecture-based teaching to interactive, discussion-oriented small group sessions with faculty and hands-on workshops that hone the trainees' critical thinking and technical skills. SNTP trainees have multiple opportunities to interact with physician scientists through coursework, collaborative research projects, and one-on-one interactions with clinicians. The latter activity represents a new initiative that provides SNTP trainees with an opportunity to learn about diseases most relevant to their thesis work. Trainees also benefit from a Career Paths seminar series that exposes them to the diverse post-PhD career options available and to help them start a personal contact network. Annual research seminars by trainees hone their presentation skills and reinforce the highly interactive environment that characterizes the Tufts neuroscience community. SNTP trainees are capable, proactive, and motivated scientists, as evidenced by awards, presentations at national meetings, and student-led outreach activities that include teaching workshops at high schools and colleges with large populations of students from underserved groups. The SNTP provides trainees with the solid multifaceted foundation they need to build successful research careers and contribute to knowledge of both healthy and diseased nervous systems.